- 學位論文
溫度應答型藥物載體微胞之合成及其降解性與生物相容性探討
Synthesis of thermal response based drug carrier micelles and its biodegradability and biocompatibility studies
摘要
本研究的目標為合成可生物降解及可溫度應答微胞，以之包載及釋放藥物。首先，以總體聚合法製備生物可降解之聚琥珀酸亞胺(PSI)，繼以NIPAAm和DMAAm聚合成溫度應答之高分子(poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide), PND)，再將PSI和PND聚合成可生物降解及可溫度應答微胞(PND-g-PAsp)。PSI、PND和PND-g-PAsp都經由FT-IR和1H-NMR確證成功合成。這些聚合物由GPC檢測得的多分散性指標值皆小於1.7。TEM及DLS對PND-g-PAsp之平均粒徑分析結果分別為110 nm與195 nm，屬微胞尺寸。PND-g-PAsp之低臨界溶液溫度為41.9 ℃，在水中之分散性極佳，其臨界微胞濃度值為0.33wt%，咖啡因釋放結果顯示於45 ℃環境下，12小時後微胞可釋放咖啡因97 μg，釋放速率約為8.08 μg/小時。此外，PND-g-PAsp對L929細胞株之於MTT試驗結果顯示，此微胞具有良好之生物相容性。PND-g-PAsp在磷酸鹽緩衝溶液的環境中，56天之降解率可達51.69%，pH值則由7.4降至7.1。總言之，本研究已成功製備出符合人類體溫之可溫度應答及可生物降解載體微胞，除了具有生物相容性之外，亦有攜藥及釋放藥物之能力，已具有生醫應用之可行性。
並列摘要
The goal of this study is to synthesize biodegradable and thermoresponsive micelles for carrying and releasing drugs. The bulk polymerization method was used to synthesize biodegradable polysuccinimide (PSI) first. The thermoresponsive polymer (poly(N-isopropylacrylamide-co-N,N- dimethylacrylamide), PND) was then obtained by mixing NIPAAm and DMAAm together. Lastly, synthesizing the micelles (PND-g-PAsp) that possess biodegradability and thermoresponsibility was carried out by polymerizing PND to PSI. The structures of these three polymers were verified by the 1H-NMR spectroscopy. The FT-IR spectroscopy confirmed that the PND-g-PAsp contains aspartic acid, NIPAAm, and DMAAm. The GPC showed that the polydispersity indexes of these polymers were all less than 1.7. The size of the PND-g-PAsp micelles was examined by TEM and DLS; and the results show that the average diameters of the micelles were 110 and 195 nm, respectively. The experiments showed that the PND-g-PAsp micelles had lower critical solution temperature of 41.9 ℃, could be fully dispersed in double distilled water and had the critical micelle concentration value of 0.33wt%. The experiments also showed that the PND-g-PAsp micelles were able to load caffeine. yet release caffeine of 97 μg in a period of 12 hours at the temperature of 45 ℃. This implies that the releasing rate was 8.08 μg/hour approximately. While in performing in vitro study of a cell line of mouse fibroblasts, L929, the MTT assay results indicated that the PND-g-PAsp micelles are cyto-toxicity free. In PBS the micelles degradation rate was 51.69% in a period of 56 days, and its pH value was down from 7.4 to 7.1. In conclusion, this work has successfully polymerized the PND-g-PAsp micelles that have the ability to carry and release drugs; yet they are thermoresponsive, biocompatible and biodegradable. It is believed that the PND-g-PAsp micelles have the feasibility for biomedical applications.